1. Field of the Invention
This invention relates to analytical measurement and in particular to electrodes for determining specific ion concentrations in solution. More specifically, this invention relates to multilayer elements for use in the potentiometric determination of ion concentrations in aqueous liquids, particularly body fluids such as blood sera.
2. Description of Related Art
The related art is replete with a great variety of electrode types and structures for the measurement of various ions in solution. Typically, devices for obtaining such measurements include a reference electrode and a separate ion-selective electrode. When simultaneously immersed into the same body of solution to be analyzed, the reference and ion-selective electrodes constitute an electrochemical cell, across which a potential develops. This potential is proportional to the logarithm of the activity of the ion of choice which is related to concentration in the solution of the ion of choice to which the ion-selective electrode is sensitive. The foregoing relationship between the potential and ionic activity in solution is described by the well-known Nernst equation. An electrometric device, usually either a direct reading circuit or a null-balance potentiometric circuit, is employed for measuring the potential between the electrodes.
In the past, the ion-sensitive electrode generally comprised an electrode body (usually same type of glass container) containing a known reference solution in contact with a half-cell of known potential, generally Ag/AgCl/"XMCl" and an ion-selective glass membrane mounted in an aperture in the electrode body in such a fashion that, when the electrode was immersed in the unknown solution, the glass membrane contacted both the reference solution within the electrode body and the unknown solution. An appropriate metal probe coated with a layer of an insoluble salt of the metal immersed in the contained reference solution served as the contact while providing a reference potential for the electrode. The selectivity of the electrode was determined by the composition or components of the glass membrane. Such electrodes are referred to herein as "barrel" electrodes. U.S. Pat. Nos. 3,598,713 and 3,502,560 provide detailed descriptions of electrodes of this type.
More recently, the development of synthetic, polymeric ion-selective membranes as substitutes for the ion-selective glass membrane has broadened the list of ions which can be determined potentiometrically using "barrel" electrodes. Such membranes generally comprise a polymeric binder or support impregnated with a solution of an ion-selective carrier or ionophore in a solvent for the ionophore. Membranes of this type can be custom-designed to sense selectively a particular ion by careful selection of the ionophore, solvent, etc. Membranes of this type and "barrel" electrodes containing such membranes as substitutes for the glass membranes are described in detail in the following U.S. Pat. Nos.:
3,562,129 to Simon issued Feb. 9, 1971, PA1 3,691,047 to Ross et al issued Sept. 12, 1972, and PA1 3,753,887 to Kedem et al issued Aug. 21, 1973. PA1 (1) cost: generally a single electrode costs several hundred dollars; PA1 (2) fragility: the body and the membrane of glass electrodes are fragile; and PA1 (3) reproducibility: even with the most carefully preformed conditioning procedures, after the first use of the electrode to determine the ionic activity of unconditioned fluids such as body fluids, the exact composition of the electrode membrane (glass or polymeric) is unknown due to the potential for contamination by earlier test solutions, and for this reason the results are often suspect.
The principle advantage of the ion-selective "barrel" electrodes, in addition to their high specificity is that if certain rigid conditioning procedures are applied between measurements, the electrode can be used repeatedly for measuring the concentration of the same ion in different solutions.
The major shortcomings of some conventional ion-selective electrodes include:
In an attempt to solve some of the foregoing problems, Cattrall, R. W., and Freiser, H., Anal. Chem., 43, 1905 (1971), and James, H., Carmack, G., and Freiser, H., Anal. Chem., 44, 856 (1972), described calcium ion-selective "coated wire" electrodes comprising a platinum wire coated with a layer of a polyvinyl chloride solution of, for example, calcium didodecylphosphate (see also British Pat. No. 1,375,785 published Nov. 27, 1974). These authors make no mention of the use of an internal reference electrode or an internal reference solution and, in fact, specifically exclude these components. These electrodes are evaluated in Stworzewicz, T., Cyapkiewicz, J., and Lesko, M., "Selectivity of Coated Wire and Liquid Ion-Selective Electrodes" at the Symposium on Ion-Selective Electrodes at Mutrafured, Hungary, October, 1972 (Proceedings reported in Ion-Selective Electrodes, edited by Pungor, E., Budapest, 1973, at pp. 259-267). The electrodes exhibit significant drift in electrical potential which requires frequent restandardization and hence makes their commercial use difficult.
Other known ion-selective electrodes are the reference and hydrogen ion-selective electrodes described in U.S. Pat. Nos. 3,833,495 issued Sept. 3, 1974 and 3,671,414 issued June 20, 1972, both to W. T. Grubb. These electrodes use a silver-silver halide reference electrode immersed in a thickened reference solution of a suitable "solvent medium," for example agar, carboxymethyl cellulose, polyvinyl alcohol, etc., and an ionic salt, e.g., KCl, in a shrinkable tube structure open at one end to the solution to be tested. In use, the reference solution contacts the solution under test directly with no intervening ion-selective membrane. The reference solution contains substantial quantities of water as evidenced by the fact that the recommended procedure for preparing the electrode involves injecting the electrolyte into the structure using a syringe.
French Patent Publication No. 2,158,905 published June 15, 1973, describes an ion-selective electrode which utilizes as the internal reference electrolyte solution a solution of a suitable salt (e.g., KCl) in a hydrated methylcellulose gel or, alternatively, a hydrophobic polystyrene ion-exchange resin overcoated with an ion-selective membrane comprising, for example, an organo polysiloxane or polycarbonate binder having a suitable ion carrier, for example, valinomycin dissolved or dispersed therein. The internal reference electrode described in this element comprises a metal wire (e.g., Ag) having a controlled coating of salt (e.g., AgCl) thereon. Whichever of the two alternative reference electrolyte materials is used (i.e., the gel or the ion-exchange resin), it is "hydrated" prior to application of the overlying ion-selective membrane.
In the case of hydrophobic ion-exchange materials prepared as described in U.S. Pat. No. 3,134,697 to Niedrach which is cited in French Pat. No. 2,158,905 as disclosing the preparation of such materials, the water content of these ion exchangers is between 15 and 50 percent. As is recognized by the skilled artisan, this water of hydration can be removed from such ion-exchange materials only with great difficulty.
U.S. Pat. No. 3,730,868 to Niedrach issued May 1, 1973, describes a carbon dioxide-sensitive electrode which uses a silver/silver halide internal reference electrode and a quinhydrone electrode as a pH sensor to detect changes in pH induced by CO.sub.2 which penetrates an overcoated carbon dioxide-permeable membrane. There is no suggestion in this patent that useful electrodes can be obtained by overcoating this redox reference electrode directly with an ion-selective membrane to obtain an ion-selective electrode. Rather, an ion-exchange resin is used as an electrolyte solution to quantify variations in CO.sub.2 concentration as permitted by the CO.sub.2 -permeable membrane. The electrode is therefore similar to those described in French Pat. No. 2,158,905, except that in one aspect a solid quinhydrone electrode is used as a pH sensor.
U.S. Pat. No. 3,856,649 issued Dec. 24, 1974, to Genshaw et al and a paper by the same authors entitled "Miniature Solid State Potassium Electrode for Serum Analysis", Analytical Chemistry, 45, pp. 1782-84 (1973), describe a solid state ion-selective electrode for potassium ion detection, which electrode comprises, on a wire, an electrically conductive inner element with a salt disposed on a surface portion thereof having as a cation, a cationic form of the inner element and also having an anion, a solid hydrophilic layer in intimate contact with the salt and including a water-soluble salt of the anion and a hydrophobic layer in intimate contact with the hydrophilic layer whereby the hydrophilic layer is shielded from contact with the ion-containing aqueous solution under test when the electrode is immersed therein. The patent refers to the importance of maintaining the electrode in a "hydrated" state during the course of manufacture and states at column 3, lines 27-29, "This hydrated state is considered important to the proper functioning of the electrode of this invention."
Although the Genshaw et al patent makes no specific and clear reference to it, the publication clearly states, and applicants have found in their evaluations of such electrodes, as demonstrated in the examples below, that, if accurate and reproducible results are to be obtained, electrodes of this type must be hydrated prior to use if stored dry (i.e., under ambient conditions, RH 40-50%) for extended periods after manufacture. Such hydration requires that the electrodes be stored in an aqueous solution or preconditioned in an aqueous solution prior to use in an ion-activity-determining operation. Failure to use such preconditioning or storage techniques will result in the generation of non-Nernstian responses which exhibit substantial random drift as described hereinafter, at least until such time as the electrode is hydrated by the sample solution. Furthermore, if the electrode is used in a "dry" or unpreconditioned state to quantify ions in a small sample of liquid (on the order of less than about 100 .mu.l), the absorption of the substantial amounts of water which are necessary to bring the wire electrode to equilibration may result in a substantial change in the actual ion concentration before a reproducible potentiometric reading can be obtained.
Thus, although the "solid-state" electrodes described by Genshaw et al offer substantial advantages of size and the quantity of sample required for measurement, as compared with electrodes of the prior art, they retain one very significant shortcoming; namely, they must generally be either stored "wet" or hydrated (i.e., preconditioned) for some period prior to use.
Israeli Pat. No. 35,473 entitled "Ion-Specific Measuring Electrodes" describes an ion-selective electrode comprising an ion-selective membrane in conducting contact with a "conductive solid material," namely graphite, (particulate or solid) which in turn contacts a wire lead for the electrode. No reference solution or redox couple is described or suggested.
U.S. Pat. Nos. 3,649,506 and 3,718,569 issued Oct. 14, 1969 and Feb. 27, 1973 respectively "solid-state" glass electrodes in which a conductor having a surface layer of an electrochemically active metal is coated with a first coating of a mixture of a glass and a halide of the active metal and a second outer coating of non-sensitive glass. Presumably such electrodes require the same preconditioning techniques as conventional glass electrodes.
U.S. Pat. No. 3,900,382 issued Aug. 19, 1975 describes a miniaturized electrochemical electrode which functions as both an oxygen or carbon dioxide electrode and an ion-selective electrode. At Column 2, lines 43-53 it is suggested that the various layers could be applied by dipping the metal wire core of the electrode in various organic solutions after which each solution solvent was evaporated. Quite obviously this description cannot apply to the "electrolyte layer" designated 17 which comprises a solution of sodium bicarbonate and sodium chloride with a thickening agent. Such a layer could not be provided from an "organic solution" and hence the suggestion as to manufacture is inapplicable. Furthermore, at Column 4, lines 49-58 the electrolyte is explicitly described as an aqueous solution.